Inhalable Polymeric Microparticles for Phage and Photothermal Synergistic Therapy of Methicillin-Resistant Staphylococcus aureus Pneumonia

Nano Lett. 2024 Jul 17;24(28):8752-8762. doi: 10.1021/acs.nanolett.4c02318. Epub 2024 Jul 2.

Abstract

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.

Keywords: MRSA pneumonia; phage; photothermal therapy; porous PLGA microspheres; synergistic therapy.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteriophages / chemistry
  • Humans
  • Indocyanine Green / administration & dosage
  • Indocyanine Green / chemistry
  • Indocyanine Green / pharmacology
  • Indocyanine Green / therapeutic use
  • Methicillin-Resistant Staphylococcus aureus* / drug effects
  • Mice
  • Microspheres
  • Phage Therapy / methods
  • Photothermal Therapy
  • Pneumonia, Staphylococcal / therapy
  • Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Indocyanine Green
  • Anti-Bacterial Agents